We found that the measurement of serum (CT) at basal levels and after pentagastrin stimulation was the most reliable method for detection of medullary thyroid carcinoma (MTC), but not for detection of patients who carry the disease while in the pretumorous stage. Our aim is to use the cytogenic analysis to identify the phenomenon of genetic instability in patients and family members as a second marker to predict the possibility of neoplastic development. We found that in cultured lymphocyte samples taken from MTC patients, the chromosomes exhibited a relatively higher frequency of spontaneous aberrations (average 10.2 + 3.1% metaphases). The close relatives of three families with high CT levels and surgical neoplastic findings showed such a trait. In lymphocytes of normal persons, chromosome aberrations, usually of chromatid type, are rarely encountered (average about 3.2 + 1.6%). Our studies showed: (1)\that patients with MTC have an increased spontaneous chromosomal aberration rate (SCAR), in brief a chromosomal instability (CI); (2)\increased chromosomal aberration in family members with multiple endocrine neoplasia type IIa (MEN-IIa) kindreds; (3)\such patients with high SCAR should be tested with CT measurement at basal levels and after stimulation; (4)\if serum CT is high, thyroidectomy should be considered; (5)\if CT is low, the patient should be followed at regular intervals; and (6)\SCAR is a useful practical marker; it may be used in screening, especially where pentagastrin studies are impractical, as with children. (5)